The extracellular matrix (ECM) is a complex network of structural and functional proteins that form tissue-specific architectures. The ECM includes secreted products of resident cells in each tissue and organ. The matrix molecules include structural and functional proteins, glycoproteins, and glycosaminoglycans. The resident cells of the ECM, besides produce ECM, receive signals therefrom, allowing for tissue development and/or homeostasis. Those properties are the basis for the use of ECM-based materials in tissue engineering and regenerative medicine. Because ECM provides a naturally occurring and highly conserved substrate for cell viability and growth that has reduced immunogenicity, ECM-based substrates having individual ECM components or of whole decellularized tissues have been used in a wide range of applications in both preclinical and clinical settings.